09.23.2025

Advanced Parkinson’s Disease: Considerations for Patient Management in Transition to Hospice Services

BACKGROUND ON PARKINSON’S DISEASE

Parkinson’s disease (PD) is a degenerative central nervous system disorder resulting from degeneration of dopamine-producing neurons in the section of the midbrain called the substantia nigra. Dopamine depletion from the basal ganglia (the central defect in PD) results in major disruptions in the connections to the basal ganglia, motor cortex, and other brain areas, including the cerebellum, leading to the hallmark Parkinsonian symptoms of tremor, rigidity, bradykinesia, and gait and balance difficulties.1,2

PD is more than a movement disorder, however; it is a lifelong, progressive condition that affects every aspect of a person’s physical, cognitive, and emotional function. From the first subtle tremor to the complex interplay of motor fluctuations and dementia in advanced stages, PD reshapes daily life for patients and their caregivers. Autonomic dysfunction (gastrointestinal symptoms, dysphagia, orthostatic hypotension, diaphoresis, urinary difficulties) was previously only reported in advanced disease, however evidence now shows that these symptoms are seen in the early stages of PD and can sometimes precede motor symptom occurrence.13

While many people live with Parkinson’s for many years after diagnosis, the journey is rarely linear.1 Over time, the balance shifts from managing symptoms and maintaining independence to prioritizing comfort, dignity, and quality of life. For patients in the late stages of PD, the physical and emotional demands can be immense. Severe rigidity, frequent “off” periods, hallucinations, aspiration pneumonia, and profound fatigue are common. In the transition to comfort measures, hospice teams can help manage the unique symptom burden of PD, avoid harmful medication changes, and provide supportive services to caregivers.

PROGRESSION TO ADVANCED PARKINSON’S DISEASE

Parkinson’s disease (PD) progression is highly variable and patient-specific. However, recognizing when a patient may be approaching the end of life can help prioritize preparation for future needs and support. Though there is no validated predictive tool for end-of-life prognostication for PD, the following relative criteria have been suggested by a Parkinson’s Foundation-sponsored work group to guide when a referral to hospice services is indicated:3

  1. Advanced disease:
  • Critical nutrition impairment in the past year has led to 10% weight loss over 6 months or BMI<18 and the refusal of artificial feeding
  • Life-threating complications in the past year (recurrent aspiration pneumonia, falls with fractures, sepsis, pyelonephritis, recurrent fever, or stage 3 or 4 pressure ulcers)
  • Motor symptoms that are poorly responsive to dopaminergic medications such as carbidopa/levodopa (Sinemet®), or cannot be treated with dopaminergic medications due to unacceptable side effects, and result in significant impairments in self-care ability
  1. Disease progression:
  • Rapid or accelerating motor (gait, balance) and non-motor symptoms (severe dementia, dysphagia, bladder dysfunction, stridor in multiple system atrophy)
  • Dependent with most Activities of Daily Living (ADLs)
  1. Advanced dementia:

Approximately 40% of PD patients develop dementia and,1 when severe, dementia symptoms can surpass the motor features of PD as the main cause of disability and mortality.4

In a patient’s transition to comfort measures, it is important that an individualized plan of care is crafted with Parkinson’s-specific considerations. The hospice team may also consider consulting with the patient’s neurologist, when feasible, to help ease the transition to hospice care.

FOSTER MEDICATION CONTINUITY3,5

In advanced Parkinson’s disease, levodopa remains the cornerstone of comfort-focused care. Abrupt discontinuation of levodopa or dopamine agonists may cause severe rebound rigidity, hyperthermia, and Dopamine Agonist Withdrawal Syndrome (DAWS) (anxiety, panic attacks, depression, sweating, nausea, pain, fatigue, dizziness, and intense craving for the medication). Recommendations include:

  • Do not stop levodopa suddenly
  • If the patient can no longer swallow safely, consider alternate routes of administration such as:
    • Enteral administration of carbidopa/levodopa (Sinemet®) (crushed regular-release tablets or suspension) via PEG tube, where available
    • More costly alternatives:
      • Orally disintegrating tablets (Parcopa®)
      • Transdermal rotigotine (Neupro®) (use cautiously—may increase risk of terminal delirium)
      • Subcutaneous apomorphine (Apokyn®) injections for severe terminal stiffness
  • When levodopa taper is unavoidable due to severe hallucinations not manageable by dose adjustment(s), reduce slowly over 2–3 weeks and monitor for withdrawal or worsening rigidity. It’s important to find a balance between managing common Parkinsonian symptoms and avoiding the troublesome side effects of levodopa.
  • Consult a neurologist for individualized tapering schedules to maintain maximum comfort.

MANAGE ON/OFF FLUCTUATIONS

“On/off” fluctuations describe alternating periods where Parkinson’s medications are effective or “on” (improved mobility, reduced rigidity) and ineffective or “off” (severe stiffness, tremor, freezing of gait). In late disease, the brain’s ability to store and buffer dopamine is diminished, and the therapeutic window narrows, making timing and formulation critical.6

Recommendations:6

  • Simplify the dosing regimen: Instead of multiple small doses, use fewer doses with a longer-acting formulation.
  • Combine oral and transdermal therapy to provide more consistent medication levels, lessening peak and trough concentrations.
  • Introduce observation logs to caregiver to help identify periods of activity (e.g., meals, transfers) for timing medication administration.
  • Avoid missed doses, as even one skipped dose can cause prolonged “off” time in advanced disease.
  • Recognize the limitations of adjunct therapy in the management of motor fluctuations:
    • These therapies usually include dopamine antagonists such as catechol-o-methyltransferase (COMT) inhibitors like entacapone (Comtan®) or MAO-B inhibitors like rasagiline (Azilect®).3
    • Adjunct dopaminergic  therapies may cause or worsen dyskinesia and nonmotor dopaminergic side-effects due to overstimulation of dopamine receptors and can also exacerbate neuropsychiatric symptoms.

In advanced stages of disease progression, managing the complexities of Parkinson’s medications can be challenging. Hospice interdisciplinary team collaboration, in consultation with the patient’s primary physician and/or neurologist, is integral for optimal care on hospice admission and with every medication change.5 (See Parkinson’s Disease Symptom Management: Converting Between Common Products – Enclara Pharmacia7)

CONTROL PAIN

Painful sensory symptoms are reported in up to half of patients with PD. While pain usually correlates with motor fluctuations, it can also be related to secondary diseases which are only amplified due to motor and non-motor symptoms.4

Types of pain in advanced PD:8

  • Somatic and visceral pain from motor fluctuations (rigidity, immobility, posture, sustained muscle contractions)
  • Neuropathic pain from nerve compression or peripheral neuropathy
  • Central pain (burning or aching) caused by brain-based pain processing changes

A fundamental approach in PD-related pain is optimizing dopaminergic therapy. Doing so will reduce pain caused by insufficient dopaminergic supply (akinesia and/or rigidity), oversupply of dopaminergic therapy (dyskinesia and/or dystonia), or central pain that is dopamine sensitive.8 Other symptom management approaches include:

  • Musculoskeletal pain can be treated with medications such as NSAIDS including ibuprofen (Motrin®) or diclofenac (Voltaren®), or COX-2 inhibitors like celecoxib (Celebrex®). Opioids like morphine (MSIR®) can also be used for musculoskeletal pain unrelieved by other treatment options.
  • For neuropathic pain, medications such as pregabalin (Lyrica®) and gabapentin (Neurontin®) are frequently used.
  • For central pain, opioids are frequently used, including oxycodone (OxyIR®), morphine (MSIR®), or hydromorphone (Dilaudid®).
  • Non-pharmacologic support such as gentle stretching, warm compresses, proper positioning, and soft tissue massage can also be helpful.

ANTICIPATE AND MANAGE PSYCHOSIS

Up to 40% of advanced PD patients develop psychosis, often with visual hallucinations or delusional thinking. Assessment and treatment of psychosis is similar to that of delirium.9 Several PD medications can also be the primary cause of psychosis including amantadine (Symmetrel®), MAO-B inhibitors like rasagiline (Azilect®), COMT inhibitors like entacapone (Comtan®), and dopamine antagonists like pramipexole (Mirapex®). It is important to first assess for offending medications before initiating additional medication(s).9

Avoid dopamine-blocking agents that could worsen Parkinsonian symptoms:10

  • Haloperidol (Haldol®), which is common in hospice comfort kits, can cause severe, irreversible motor worsening
  • Olanzapine (Zyprexa®) can place the patient at considerable risk of sedation and worsening motor symptoms
  • Metoclopramide (Reglan®) can worsen motor symptoms

Preferred antipsychotic medications:

  • Quetiapine (Seroquel®) is well-tolerated with minimal effect on motor function. It is recommended to start at a low dose such as 12.5mg-25mg to limit somnolence9,10
  • Pimavanserin (Nuplazid®) is designed for PD psychosis but can be cost prohibitive10
  • Clozapine (Clozaril®) is also effective but can cause severe neutropenia leading to serious infections9-11

MANAGING COMMON AUTONOMIC DYSFUNCTION SYMPTOMS

Gastrointestinal

Constipation is one of the most common GI symptoms seen in PD with around half of all patients experiencing this condition.12 Patients often have increased severity in constipation during later disease stages.13 Management includes:

  • Non-pharmacologic interventions such as increased fiber and water intake along with exercise and mobility, as tolerated.12
  • Medication review and intervention:
    • Levodopa is a beneficial medication for treatment of motor symptoms as well as dysphagia in PD, however it is not as useful for the treatment of constipation.
    • Some patients have found beta-blockers such as metoprolol, carvedilol, and propranolol are able to significantly lower the risk of constipation. In the general population beta blockers can cause constipation however, in PD there is often the opposite effect which is believed to be related to beta-blockade on a dysregulated autonomic nervous system.12

Nausea can result from dopaminergic therapy, slowed gastric emptying (gastroparesis), constipation, or disease progression affecting brainstem nausea centers. Management includes:

  • Supportive strategies:
    • Encourage small, frequent meals
    • Manage constipation aggressively with laxatives such as polyethylene glycol (MiraLAX®) or senna (Senokot®) and by staying properly hydrated
    • Adjust timing of Parkinson’s medications in relation to meals to reduce GI side effects
  • Medication therapy:10
    • Ondansetron (Zofran®) working via serotonin (5-HT3) blockade, does not worsen PD symptoms and is well tolerated
  • Medication review and intervention:3
    • Metoclopramide (Reglan®) is a centrally acting dopamine antagonist that can significantly worsen motor symptoms
    • Prochlorperazine (Compazine®) causes dopamine blockade and can increase the risk of rigidity and motor decline
    • Haloperidol (Haldol®) is often used in hospice for nausea but is contraindicated in PD

Dysphagia

Dysphagia can occur from progression of PD and/or dementia, increasing the risk of aspiration pneumonia. Interventions can include:1

  • Speech-language pathology (SLP) evaluation for individualized swallow strategies
  • Diet modifications: puree or mechanical soft textures, nectar or honey-thick liquids
  • Upright positioning during and at least 30 minutes after meals
  • Teaching caregivers safe feeding pace and the chin-tuck technique where the patient moves their head and chin back
  • Medication formulation changes (liquid suspensions, orally disintegrating tablets)

Orthostatic Hypotension

Orthostatic hypotension is a common issue seen with PD with a prevalence of about 60%. Nonpharmacologic interventions are recommended as first line treatment. Pharmacologic interventions can be added for orthostatic hypotension unresponsive to nonpharmacologic treatment. Examples include:9

  • Increased fluid or salt intake
  • Compression stockings
  • If medically appropriate, decrease anti-hypertensive medications
  • For refractory cases, consider midodrine (ProAmatine®) or fludrocortisone (Florinef®)

Urinary Difficulties

Urinary dysfunction is seen in more than 50% of patients with PD. The most common urinary symptoms are categorized as storage symptoms and include the need to urinate frequently and trouble delaying urination once the need is perceived, creating a sense of urinary urgency (e.g., nocturnal urine, incontinence). Less frequently occurring, but still troubling, are voiding symptoms including delays in initiating urination and poor urine stream.12 Urinary frequency and urgency can be managed with:

  • Lifestyle modifications (e.g., reduce intake of caffeine and alcohol, avoid fluids before bedtime), scheduled (prompted or timed) bladder emptying, and effective management of constipation15
  • Medication therapy: Beta-3 adrenergic agonists (e.g., mirabegron (Myrbetriq®), vibegron (Gemtesa®)) and antimuscarinics (e.g., oxybutynin (Ditropan®), tolterodine (Detrol®), solifenacin (Vesicare®), darifenacin (Enablex®)).10,14

EDUCATE CAREGIVERS

Caregiver skill directly impacts patient safety, comfort, and quality of life. Key teaching points include:

  • Medication administration timing to minimize “off” periods
  • Recognizing early signs of aspiration, infection, or pain
  • Managing hallucinations without confrontation
  • Safe transfer techniques to prevent injury to patients and caregivers
  • Using adaptive equipment (hospital bed, lift devices, non-slip mats)
  • Emotional support and respite resources to reduce burnout

CONCLUSION

This article highlights the need for disease specific hospice planning in advanced Parkinson’s disease. Maintaining dopaminergic therapy, preventing withdrawal, and addressing unique motor and non-motor symptoms are key to maximizing comfort. A plan of care, neurologist-hospice collaboration, and caregiver-centered interventions ensure patients spend their final days with dignity, reduced suffering, and tailored symptom control. (For additional guidance, See Parkinson’s Disease Psychosis: Patient Case and Brief Review – Enclara Pharmacia15)

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REFERENCES

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  2. Jankovic J. Epidemiology, pathogenesis, and genetics of Parkinson disease. In: UpToDate, Hurtig HI, Eichler AF (Eds), Wolters Kluwer. (Accessed September 16, 2025)
  3. Veronese S, Richfield E. Palliative Care for Parkinson Disease and Atypical Parkinsonian Disorders. In: UpToDate, Morrison RS, Hurtig HI, Eichler AF (Eds), Wolters Kluwer. (Accessed September 9, 2025)
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  7. Parkinson’s Disease Symptom Management: Converting Between Common Products. Enclara Pharmacia. May 10, 2021. https://enclarapharmacia.com/palliative-pearls/parkinsons-disease-symptom-management-converting-between-common-products
  8. Buhmann C, Kassubek J, Jost WH. Management of Pain in Parkinson’s Disease. J Parkinsons Dis. 2020 Sep 1;10(Suppl 1):S37–S48. https://doi.org/10.3233/JPD-202069
  9. Estupinan D, Roche-Green A, Robinson M, Shannon RP. Parkinson’s Disease: Part 2 – Palliation for Common Non-Motor Symptoms. Palliative Care Network of Wisconsin Fast Facts. June 25, 2019. https://www.mypcnow.org/fast-fact/parkinsons-disease-part-2-palliation-for-common-non-motor-symptoms/
  10. Clinical Pharmacology [database online]. Tampa, FL: Elsevier/Gold Standard, Inc.; 2025.
  11. U.S. Food & Drug Administration. Drug Safety Communication. FDA removes risk evaluation and mitigation strategy (REMS) program for the antipsychotic drug Clozapine. August 27, 2025. Available from: https://www.fda.gov/drugs/drug-safety-and-availability/fda-removes-risk-evaluation-and-mitigation-strategy-rems-program-antipsychotic-drug-clozapine?utm_medium=email&utm_source=govdelivery
  12. Pasricha TS, Guerrero-Lopez IL, Kuo B. Management of gastrointestinal symptoms in Parkinson’s disease: a comprehensive review of clinical presentation, workup, and treatment. J Clin Gastroenterol. 2024 Mar 1;58(3):211-220. https://doi.org/10.1097/mcg.0000000000001961
  13. Asahina M, Vichayanrat E, Low DA, et al. Autonomic dysfunction in parkinsonian disorders: assessment and pathophysiology. J Neurol Neurosurg Psychiatry 2013;84:674-680. https://doi.org/10.1136/jnnp-2012-303135
  14. Factor SA, Esper CD. Multiple system atrophy: Prognosis and treatment. In: UpToDate, Hurtig HI, Eichler AF (Eds), Wolters Kluwer. (Accessed September 22, 2025)
  15. Parkinson’s Disease Psychosis: Patient Case and Brief Review. Enclara Pharmacia. May 8, 2020. https://enclarapharmacia.com/palliative-pearls/parkinsons-disease-psychosis-patient-case-and-brief-review

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